Christian G. Kohler · University of Pennsylvania · PhdFit
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Christian G. Kohler
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University of Pennsylvania · Rehabilitation Medicine
Christian G. Kohler, M.D., is a Professor of Psychiatry at the Hospital of the University of Pennsylvania. He is a neuropsychiatrist affiliated with the Brain Behavior Clinic at the University of Pennsylvania. Dr. Kohler serves as the Clinical Director of the Neuropsychiatry/Schizophrenia Research Center and is the Director of the Psychosis Evaluation and Recovery Center at UPENN. His clinical expertise includes schizophrenia, early psychosis, and neuropsychiatry, with a focus on comprehensive treatment approaches. His research expertise encompasses schizophrenia, early psychosis, social cognition, and comprehensive treatment strategies, contributing to the understanding and management of neuropsychiatric conditions.
BACKGROUND: Youth at risk for psychosis based on subthreshold positive symptoms (PS) show elevated negative symptoms such as amotivation, associated with disability and increased risk of psychotic transition. Intrinsic motivation (IM), the desire to obtain internal satisfactions such as mastery or curiosity, is more impaired in psychosis than extrinsic motivation (EM), the desire to obtain external rewards. However, the neural mechanisms underlying IM impairment in PS have scarcely been studied, and never with measures designed for this purpose. METHODS: We applied a novel fMRI fractal memory task that leveraged distinct feedback conditions designed to engage IM and EM processes, along with self-reported IM and EM, in adolescents and young adults with PS (n = 95) and healthy controls (CT, n = 31). RESULTS: We hypothesized that IM would generate reinforcement signals in the ventral striatum (VS), a core motivation region, as individuals internally evaluated their performance relative to their expectations. We further hypothesized that reduced VS activation would relate dimensionally to lower self-reported IM across both PS and CT groups. Consistent with these hypotheses, VS and related motivation circuitry preferentially activated to higher confidence task choices and to reward prediction error during performance feedback. VS activation during task choices related selectively to IM but not EM. CONCLUSIONS: Our findings highlight the role of VS in encoding self-generated reinforcement signals, and demonstrate a selective relationship between VS activation and IM. Understanding the link between VS dysfunction and impaired IM will facilitate therapeutic advances to remediate IM deficits in those at risk for psychosis.
Early Intervention in Psychiatry · 2025-04-01 · 3 citations
articleOpen access
AIM: Connection Learning Healthcare System, one of the eight hubs of the National Institute of Mental Health funded Early Psychosis Intervention Network, supports uniform data collection, analysis, feedback and infrastructure development to promote a culture of continuous quality improvement across 25 Coordinated Specialty Care programs serving young people experiencing first episode psychosis and their families in Maryland and Pennsylvania. This first report describes the hub and its constituent programs, the approach for developing and implementing a hub-wide core assessment battery harmonised with the national battery, and preliminary program and participant characteristics. METHODS: Our hub developed and implemented a computerised core assessment battery, administered every 6 months and developed an integrated system for managing and analysing data. RESULTS: Between 1 January 2021 and 27 November 2023, 1059 participants were newly admitted to a hub program. The entire cohort (N = 1381) included newly admitted participants and those already in a program as of 1 January 2021. A total of 1245 complete assessment batteries were collected across all time points from 797 participants, with an additional 1920 partially completed batteries collected from 1319 participants. Data are uploaded to the National Data Coordinating Center, where our hub is the third largest data contributor. Descriptive information on programs and participants is provided. CONCLUSIONS: As part of our learning healthcare system to improve clinical services and outcomes across two states, we have successfully implemented a standardised, computerised core assessment battery of essential characteristics and clinical outcomes. Successes, challenges and recommendations for data collection are provided. This paper will serve as a vital methodological resource for users of the unprecedented Early Psychosis Intervention Network national research database seeking to accelerate and improve early psychosis research.
bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-09
preprintOpen access
Abstract Cannabis use is linked to elevated psychosis risk, yet the neurobiological mechanisms that couple use to symptom expression remain unclear. Because glutamatergic dysregulation has been implicated in both cannabis effects and psychosis vulnerability, we examined whether brain glutamate relates to dimensional symptoms as a function of cannabis use across the psychosis spectrum. Seventy-nine participants—typically developing controls, clinical high-risk individuals, and patients with psychosis—completed dimensional clinical assessments, detailed cannabis surveys, urine toxicology, and ultra-high-field 7T 1 HMRS quantification of anterior cingulate cortex (ACC) glutamate levels. Linear models assessed the main and interactive effects of ACC glutamate and cannabis use on positive and negative symptoms. Self-reported cannabis use showed strong concordance with urine toxicology. Cannabis use was associated with higher positive and negative symptoms. Independently, higher ACC glutamate predicted greater positive and negative symptoms. Notably, lower glutamate levels were associated with higher positive symptoms in cannabis users. Exploratory analyses suggested interactions for depressive and manic symptoms, indicating that glutamatergic abnormalities may amplify the overall severity of cannabis-related symptoms. Sensitivity analyses revealed lower ACC glutamate in psychosis patients—especially cannabis users—highlighting diagnostic group differences and reinforcing the link between cannabis exposure and glutamatergic dysfunction. These findings implicate ACC glutamatergic dysfunction as a transdiagnostic correlate of symptom burden, particularly in those with psychosis who are cannabis users. Glutamate-targeted interventions and longitudinal designs will be needed to examine causal pathways linking cannabis exposure to psychosis-relevant outcomes.
BACKGROUND AND HYPOTHESIS: Improvements in screening tools for early subthreshold psychosis symptoms are needed to facilitate early identification and intervention efforts, especially given the challenges of rapidly differentiating age-appropriate experiences from potential early signs of emerging psychosis. Tools can be lengthy and time-consuming, impacting their utility and accessibility across clinical settings, and age-normed data are limited. To address this gap, we sought to develop and validate a brief, empirically derived, age-normed, subthreshold psychosis screening tool, for public use. STUDY DESIGN: Computerized adaptive test simulation was used to derive a 5-item short form with age norm equivalencies from a 12-item PRIME-Screen-Revised (PRIME-12) administered to 7053 youth (Mage = 15.8, SD = 2.7; 54% female; 33% Black). Concurrent validity was assessed (n = 758) using contemporaneous administration of the PRIME-5 and the Structured Interview for Prodromal Syndromes. Comparability of criterion-related validity of the PRIME-5, PRIME-12, and Scale of Prodromal Symptoms (SOPS) was assessed by relating scores to psychosis-risk-relevant criteria. Finally, self-report versus assessor-administered PRIME total scores were compared (n = 131) to assess their concurrent validity. STUDY RESULTS: Correlations among PRIME-5, PRIME-12, and SOPS were comparable and moderate, supporting their convergent validity. The PRIME-5 also showed comparable criterion-related validity, demonstrating similar relationships with psychosis-risk indicators as the other tools. Self-reported and assessor-administered PRIME-5 were moderately correlated. CONCLUSIONS: Public availability of a brief, age-normed, and validated screening tool-which can be assessor or self-administered-will expedite and improve early identification of youth (age 11 and older) at risk for psychosis.
Journal of the American Psychiatric Nurses Association · 2025-08-06
articleSenior author
ObjectivesThis paper describes the different modalities of Coordinated Specialty Care (CSC) in first-episode psychosis and illustrates how psychiatric nurse practitioners can fulfill important roles in the team-based effort of individualized treatment and therefore increase access to specialized care for those suffering from early serious mental illness.MethodsReview of published literature and other online resources on first-episode psychosis (FEP) and CSC, shortage of psychiatric providers, and the role of the Psychiatric Mental Health Nurse Practitioner.ResultsResults are extracted from published literature on young persons experiencing FEP within current CSC models, as well as other online resources evaluating the increasing psychiatrist shortage throughout the United States.ConclusionThis article explores the potential roles and benefits of integrating psychiatric nurse practitioners into first-episode care and advocates that their involvement improves access to timely and effective interventions for young persons experiencing new-onset psychosis.
Despite decades of research, cognitive impairment remains a critical untreated symptom for many patients with schizophrenia. One way to accelerate the development of pro-cognitive therapies for schizophrenia is to evaluate compounds using biomarker approaches tailored to relevant neural mechanisms. While D1/D5 receptor (D1R/D5R) agonism has been extensively studied in neuroscience, its therapeutic potential for cognitive impairment in schizophrenia remains untapped. The Translational Neuroscience & Computational Evaluation of a D1R Partial Agonist for Schizophrenia (TRANSCENDS) clinical trial tests this mechanism using a 'target engagement' approach. Multiple, double-blind doses of a D1/D5R partial agonist were administered in advance of a functional neuroimaging (fMRI) session that deployed a cognitive paradigm explicitly designed to capture a translational micro-circuit mechanism underlying spatial working memory in patients with schizophrenia. Specifically, this study will assess whether the D1R/D5R partial agonist CVL-562 induces a dose-dependent engagement of spatial working memory circuits in schizophrenia using fMRI. This design, and the use of spatial working memory neural circuits as a dependent measure, was selected on the basis of a translational and computational understanding of prefrontal micro-circuitry and a mechanistic understanding of the role of D1R/D5Rs in schizophrenia. To enhance data integration and scalability, TRANSCENDS employs an automated informatics framework for seamless neuroimaging data sharing and electronic clinical data capture. This ensures high-standards for regulatory compliance, data quality, and data sharing across sites, improving aspects of current clinical trial data management. We share the study design and approach with the goal of advancing future pro-cognitive drug development and strategies for developing mechanistically-driven biomarkers in psychiatry.
